The object of this project is to determine how selected chemicals applied to the oral mucosa lingual stimulate lingual and buccal branches of the trigeminal nerve. The epithelial pathways by which chemicals gain access to the nerve fibers and, in turn, the transduction mechanisms by which they activate the nerves will be investigated in rats using electrophysiological and morphological techniques, and computer simulations. It is hypothesized that the activity of chemoreceptive trigeminal fibers depends on the ionic composition of the periaxonal and intra-axonal spaces. Information from these studies will elucidate the peripheral neural mechanisms underlying trigeminal chemosensitivity and should thus contribute to the understanding and treatment of those taste disorders which involve the trigeminal nerve.The epithelial pathways traversed by chemical stimuli will be distinguished by recording lingual and buccal nerve responses following mucosal application of hydrophilic (e.g. salts, acids) and hydrophobic (e.g. n-alcohols) substances and then determining to what extent lanthanum - which inhibits transport through paracellular pathways, and amiloride - which inhibits transport through transcellular pathways, affects these responses. In addition, the effect of lanthanum and amiloride on lingual nerve responses elicited by electrical stimulation of the tongue will be investigated. Neural mechanisms will be investigated in single-unit lingual and buccal nerve recordings with characterization of fibers according to their receptive field, conduction velocity, action-potential shape and responses to mechanical, thermal, nociceptive or hydrophilic and hydrophobic chemical stimuli. Whole-nerve and single-unit recordings of chemically-elicited responses after enzymatic removal of the lingual epithelium will also be undertaken. Comparisons of single-unit response parameters with those generated by a computer model of fine myelinated or unmyelinated nerve fibers (A-delta, C) will be made in order to elucidate transduction mechanisms. Trigeminal-gustatory interaction will be investigated by recording chorda tympani nerve responses to salts before and after electrical stimulation of the lingual nerve. The morphology and intra-epithelial location of nerve endings found to be chemically responsive in the single unit studies will be studied with light and electron microscopy.